Study to Compare Tivozanib in Combination With Nivolumab to Tivozanib Monotherapy in Subjects With Renal Cell Carcinoma

Renal Cell Carcinoma Clinical Trial

Official title:

TiNivo-2: A Phase 3, Randomized, Controlled, Multicenter, Open-label Study to Compare Tivozanib in Combination With Nivolumab to Tivozanib Monotherapy in Subjects With Renal Cell Carcinoma Who Have Progressed Following One or Two Lines of Therapy Where One Line Has an Immune Checkpoint Inhibitor

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04987203
• Other study ID #: AV-951-20-304
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: September 9, 2021
• Est. completion date: August 1, 2025

Study information

• Verified date: April 2024
• Source: AVEO Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will be comparing tivozanib in combination with nivolumab to tivozanib alone in subjects with advanced Renal Cell Carcinoma (RCC) who have had 1 or 2 prior lines of therapy, one of which was an Immune Checkpoint Inhibitor (ICI).

Description:

This will be an open-label, randomized, controlled, multicenter, multi-national, parallel-arm study. The study is designed to compare the progression free survival (PFS), overall survival (OS), Objective response rate (ORR), duration of response (DoR), and safety of tivozanib and the combination of tivozanib with nivolumab.

Approximately 326 subjects with refractory advanced RCC at approximately 190 sites will be randomized in a 1:1 ratio to treatment with tivozanib plus nivolumab (163 subjects) or tivozanib (163 subjects). Subjects will be randomly assigned to a treatment.

Subjects will receive 1.34 mg/day (monotherapy arm) or 0.89mg/day (combination arm) of tivozanib once daily (QD) for 3 weeks followed by 1 week off study drug. One cycle will be defined as 4 weeks: 3 weeks on treatment and 1 week off treatment. Subjects who receive nivolumab will be infused with 1 treatment of nivolumab at specified dose on specified days of each Cycle.

Subjects with documented stable disease or an objective response may continue to receive both tivozanib and nivolumab therapy at the same dose and schedule until progression as long as the tolerability is acceptable. Nivolumab will be discontinued in all subjects after 2 years; Tivozanib may be continued after discontinuation of nivolumab until other withdrawal criteria are met. A Safety Follow-up Visit will be performed 30 days (± 7 days) after the last dose of study drug.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 343
• Est. completion date: August 1, 2025
• Est. primary completion date: August 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 130 Years

Eligibility

Inclusion Criteria:

• Radiographic disease progression during or following at least 6 weeks of treatment with ICI for locally advanced or metastatic RCC with a clear cell component either in first- or second-line treatment.

• Subjects must have recovered from the adverse events of prior therapy to grade = 1 or baseline.

• Histologically or cytologically confirmed RCC with a clear cell component.

• Measurable disease per RECIST criteria Version 1.1.

• Eastern Cooperative Oncology Group performance status of 0 or 1.

• All participants must follow protocol defined contraceptive measures.

Exclusion Criteria:

• Subjects who received: a. A single agent tyrosine kinase inhibitor (TKI) in the first line setting followed by a single agent immune checkpoint inhibitor (ICI) in the second line setting; b. More than 2 prior lines of therapy in the advanced or metastatic setting.

• History of life-threatening toxicity related to prior immune therapy.

• Active autoimmune disease as well as those that required discontinuation of prior immuno-oncological (IO) therapy due to immune mediated AEs.

• Uncontrolled hypertension.

• More than 1 prior line of therapy with a checkpoint inhibitor in the metastatic setting.

• Subjects on immune suppressive therapy for organ transplant or subjects with a history of genetic or acquired immune suppression disease such as human immunodeficiency virus (HIV) [Patients with HIV who have CD4+ T-cell counts >350 cells/µL, without a history of acquired immune deficiency syndrome (AIDS)-defining opportunistic infections, and are on established antiretroviral therapy which does not include a cytochrome P450 (CYP)3A4 inducer, for at least 4 weeks and have an HIV viral load less than 400 copies/mL, are eligible].

• History of clinically significant interstitial lung disease or current non-infectious pneumonitis.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Renal Cell
• Renal Cell Carcinoma

Intervention

Drug:
• Tivozanib
Tivozanib will be administered orally.
• Nivolumab
Nivolumab will be administered via intravenous infusion.

Locations

Country	Name	City	State
Argentina	Centro Oncológico Korben	Buenos Aires	Ciudad Autónoma De Buenos Aire
Argentina	Centro Oncologico de Rosario	Rosario	Santa Fe
Argentina	Centro para la Atención Integral del paciente Oncológico	San Miguel de Tucumán	Tucumán
Argentina	Clínica Viedma	Viedma	Río Negro
Australia	Mater Misericordiae Limited	Brisbane	Queensland
Australia	Sunshine Hospital	Geelong	Victoria
Australia	Liverpool Hospital Cancer Therapy Centre	Liverpool	New South Wales
Australia	Princess Alexandra Hospital	Woolloongabba	Queensland
Belgium	Institut Jules Bordet - Oncologie Médicale	Anderlecht	Brussels Capital Region
Belgium	CHU Brugmann - Victor Horta	Bruxelles
Belgium	UZ Gent - Medische Oncologie	Gent	Oost-Vlaanderen
Belgium	Jessa Ziekenhuis - Campus Virga Jesse - Medische Oncologie	Hasselt	Limburg
Belgium	AZ Groeninge - Campus Kennedylaan	Kortrijk
Belgium	ZNA Jan Palfijn	Merksen	Antwerpen
Brazil	Universidade Estadual de Campi	Campinas	São Paulo
Brazil	Clinica de Neoplasias Litoral	Itajai	Santa Catarina
Brazil	Centro Gaucho Integrado de Onc	Porto Alegre	Rio Grande Do Sul
Brazil	Hospital Nossa Senhora da Conc	Porto Alegre
Brazil	Pontificia Universidade	Porto Alegre
Brazil	Instituto Brasileiro de Controle do Cancer - ibcc	São Paulo
Canada	Tom Baker Cancer Centre	Calgary	Alberta
Canada	Sunnybrook Research Institute, sunnybrook Health Sciences Ct	Toronto	Ontario
Canada	University Health Network - Princess Margaret Cancer Centre	Toronto	Ontario
Canada	BC Cancer - Vancouver Centre	Vancouver	British Columbia
Chile	Centro de Estudios Clinicos In	Santiago	Región Metropolitana De Santia
Chile	Centro de Estudios Clínicos SAGA SpA	Santiago	Región Metropolitana De Santia
Chile	Meditek Ltda.	Santiago de Chile	Región Metropolitana De Santiago
Chile	ACEREY Centro de Investigación Clínica Oncológica	Viña del mar	Valparaíso
Czechia	FN Hradec Kralove	Hradec Kralove
Czechia	FN Kralovske Vinohrady	Praha 10
Czechia	Fakultni Thomayerova nemocnice	Praha 4
France	Hopital Saint-Andre - Service d'Oncologie Medicale	Bordeaux	Gironde
France	CHU Michallon - Hopital Nord - Cancérologie Et Hématologie	Grenoble	Isère
France	CHD Vendee La Roche sur Yon - Gastro-Entérologie	La Roche-sur-Yon
France	Clinique Victor Hugo - Hematologie	Le Mans	Sarthe
France	Hôpital privé Le Bois	Lille	Nord
France	Centre Leon Berard - departement d'oncologie medicale	Lyon	Rhône
France	Institut Paoli Calmettes - Hôpital de jour	Marseille	Bouches-du-Rhône
France	Centre de Lutte Contre le Cancer (CLCC)	Nice
France	Hospices Civils de Lyon (HCL) - Centre Hospitalier Lyon-Sud	Pierre-Bénite	Rhône-Alpes
France	Centre Hospitalier de Poitiers	Poitiers	Poitou-Charentes
France	ICO - Site Rene Gauducheau - Oncologie Medicale	St Herblain
France	Institut de cancérologie de Strasbourg Europe - ICANS	Strasbourg	Alsace
France	Hopital Foch	Suresnes	Hauts-de-Seine
France	Hopital Trousseau - medical oncology	Tours
France	Institut de Cancérologie de Lorraine	Vandœuvre-lès-Nancy
France	Centre de Lutte Contre le Cancer (CLCC) - Gustave Roussy (Institut de Cancerologie Gustave-Roussy)	Villejuif	Île-de-France
Germany	Medizinische Hochschule Hannover	Hannover	Niedersachsen
Germany	Universitätsklinikum Heidelberg	Heidelberg	Baden-Württemberg
Italy	Ospedale S.Donato, AUSL 8 di Arezzo	Arezzo
Italy	Azienda Mater Domini	Catanzaro
Italy	P.O. Ss. Annunziata	Chieti Scalo	Chieti
Italy	PO di Cremona, ASST di Cremona - Oncologia medica	Cremona
Italy	AOUC Azienda Ospedaliero-Universitaria Careggi	Firenze
Italy	IRST	Meldola (Fc)	Forli
Italy	European Institute of Oncology	Milano
Italy	IRCCS Fondazione "Giovanni Pas	Napoli
Italy	IRCCS Policlinico San Matteo	Pavia
Italy	AO S.Camillo-Forlanini	Roma
Italy	Fondazione Policlinico Universitario Agostino Gemelli	Roma
Italy	Azienda Ospedaliera Santa Maria di Terni	Terni
Mexico	Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán	Tlalpan
Poland	Wojewodzki Szpital Specjalistyczny	Biala Podlaska
Poland	Szpital Specjalist. w Brzozowie,Podkarpacki Osrodek Onkologi	Brzozow	Podkarpackie
Poland	COPERNICUS Podmiot Leczn. Sp z o.o.,Wojew. Centrum Onkologii	Gdansk	Pomorskie
Poland	Szpital Specjalistyczny im. L. Rydygiera w Krakowie	Kraków	Malopolskie
Poland	Europejskie Centrum Zdrowia Otwock, Szpital im. F. Chopina	Otwock	Mazowieckie
Poland	Szpital Kliniczny Przemienienia Panskiego UM w Poznaniu	Poznan	Wielkopolskie
Poland	Nzoz Mrukmed Lekarz Beata Madej-Mruk I Partner Sp. P.	Rzeszow	Podkarpackie
Poland	Centralny Szpital Kliniczny Ministerstwa Spraw Wewnetrznych	Warszawa
Poland	Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy	Warszawa
Portugal	H. Prof. Doutor Fernando Fonseca	Amadora	Lisboa
Portugal	Hospital Particular do Algarve - Gambelas-Faro	Faro
Portugal	H. de Santa Maria. Centro Hospitalar Lisboa Norte - Oncologia	Lisboa
Portugal	H. Santo Antonio. Centro Hospitalar do Porto	Porto
Portugal	Instituto Português Oncologia Francisco Gentil do Porto	Porto
Spain	Hospital de La Santa Creu i Sant Pau	Barcelona
Spain	Hospital Del Mar	Barcelona
Spain	Hospital Universitario Vall d'	Barcelona
Spain	Institut Catalá d´Oncología (I.C.O.)	Barcelona
Spain	H.G.U. de Elche	Elche	Alicante
Spain	ICO-Hospital Universitari de G	Girona
Spain	Hospital Clínico San Carlos	Madrid
Spain	Hospital U. 12 Octubre	Madrid
Spain	Hospital Universitario La Paz	Madrid
Spain	Hospital Universitario Ramón y Cajal	Madrid
Spain	C.H.U. de Orense	Orense
Spain	Hospital Universitario Son Espases	Palma de Mallorca	Baleares
Spain	Hospital Universitari Parc Tau	Sabadell	Barcelona
Spain	Hospital Universitario Virgen	Sevilla
Spain	Fundación Instituto Valenciano	Valencia
Spain	Hospital Universitario Y Politécnico La Fe	Valencia	Valenciana, Comunidad
United Kingdom	Addenbrooke's Hospital - Oncology	Cambridge	Cambridgeshire
United Kingdom	Royal Derby Hospital	Derby
United Kingdom	Leeds Teaching Hospitals NHS Trust	Leeds
United Kingdom	Imperial College Healthcare NHS Trust - Hammersmith Hospital	London	London, City Of
United Kingdom	The Christie NHS Foundation Trust - Medical Oncology	Manchester
United Kingdom	Mount Vernon Cancer Centre	Northwood	England
United Kingdom	Royal Blackburn Hospital - Oncology	Preston	Lancashire
United Kingdom	Royal Marsden - Sutton	Sutton	Surrey
United Kingdom	Royal Marsden Hospital	Sutton	Surrey
United Kingdom	New Cross Hospital	Wolverhampton
United States	University of New Mexico - Comprehensive Cancer Center	Albuquerque	New Mexico
United States	Lehigh Valley Physician Group	Allentown	Pennsylvania
United States	Texas Oncology - Central Austin Cancer Center	Austin	Texas
United States	John Hopkins Medicine - Hematology/oncology	Baltimore	Maryland
United States	University of Maryland Medical Center-Greenebaum Cancer Ctr	Baltimore	Maryland
United States	St. Vincent Frontier Cancer Center	Billings	Montana
United States	Dana-Farber Cancer Institute - Medicine	Boston	Massachusetts
United States	Roswell - Roswell Park Cancer Institute - Medical Oncology	Buffalo	New York
United States	Chattanooga Oncology and Hematology Associates	Chattanooga	Tennessee
United States	Cleveland Clinic	Cleveland	Ohio
United States	Maryland Oncology Hematology	Clinton	Maryland
United States	UH Cleveland Medical Center	Columbia	South Carolina
United States	Texas Oncology - Baylor Charles A. Sammons Cancer Center	Dallas	Texas
United States	US Oncology - Rocky Mountain Cancer Centers - Midtown	Denver	Colorado
United States	Henry Ford Hospital	Detroit	Michigan
United States	City of Hope Comprehensive Cancer Center	Duarte	California
United States	Florida Cancer Specialists & Res Inst	Fort Myers	Florida
United States	Memorial Sloan Kettering Cancer Center - Westchester	Harrison	New York
United States	Chao Family Comprehensive Cancer Center, UC Irvine	Irvine	California
United States	University of California San Diego	La Jolla	California
United States	University of Kentucky UK Markey Cancer Center	Lexington	Kentucky
United States	Tennessee Oncology, PLLC	Nashville	Tennessee
United States	Vanderbilt-Ingram Cancer Center	Nashville	Tennessee
United States	Tulane Cancer Center Clinic - Oncology	New Orleans	Louisiana
United States	Memorial Sloan Kettering Cancer Center (MSKCC) - Memorial Hospital	New York	New York
United States	Oncology Hematology West PC dba Nebraska Cancer Specialists	Omaha	Nebraska
United States	Allegheny General Hospital (AGH)	Pittsburgh	Pennsylvania
United States	Leland Stanford Junior University	Redwood City	California
United States	Kaiser Permanente Riverside Medical Center	Riverside	California
United States	Florida Cancer Specialists & Research Institute (FCS) - Tampa Cancer Center Location	Saint Petersburg	Florida
United States	US Oncology Texas Oncology (CCC of South Texas) - San Antonio Medical Center	San Antonio	Texas
United States	University Of Washington - Medical Center	Seattle	Washington
United States	Northwest Medical Specialties PLLC	Tacoma	Washington
United States	Memorial Sloan Kettering Cancer Center - Nassau	Uniondale	New York
United States	The University of Kansas Cancer Center	Westwood	Kansas

Sponsors (3)

Lead Sponsor	Collaborator
AVEO Pharmaceuticals, Inc.	Bristol-Myers Squibb, Parexel

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Belgium,  Brazil,  Canada,  Chile,  Czechia,  France,  Germany,  Italy,  Mexico,  Poland,  Portugal,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression free survival	Comparison of the PFS of tivozanib in combination with nivolumab to tivozanib in subjects with RCC who have progressed following 1 or 2 lines of therapy. PFS is defined as the time from randomization to first documentation of objective tumor progression (progressive disease [PD], radiological) according to Response Evaluation Criteria In Solid Tumors (RECIST), or death due to any reasons whichever comes first.	Until progressive disease [PD] (Approximately 30 months)
Secondary	Overall Survival	Comparsion of the OS of subjects randomized to treatment with tivozanib in combination with nivolumab compared to tivozanib. OS is defined as the time from the date of randomization to date of death due to any cause.	From Screening (Days -28 to -1) until death (Approximately 42 months)
Secondary	Progression free survival	PFS is defined as the time from randomization to first documentation of objective tumor progression (progressive disease [PD], radiological) according to RECIST, or death due to any reasons whichever comes first. PFS as assessed by investigator.	Until progressive disease [PD] (Approximately 30 months)
Secondary	Objective Response Rate	Comparison of ORR of subjects randomized to treatment with tivozanib in combination with nivolumab compared to tivozanib. ORR is defined as the proportion of subjects with confirmed complete response or confirmed partial response according to RECIST relative to the total population of randomized subjects.	From Screening (Days -28 to -1) until PD (Approximately 30 months)
Secondary	Duration of Response	Comparison of DoR of subjects randomized to treatment with tivozanib in combination with nivolumab compared to tivozanib. DoR is defined as the time from the first documentation of objective tumor response to the first documentation of objective tumor progression or to death due to any cause.	From Screening (Days -28 to -1) until PD or death (Approximately 30 months)
Secondary	Number of subjects with serious and non-serious adverse events	Assessment of the safety and tolerability of tivozanib in combination with nivolumab compared to tivozanib.	From Screening (Day -28 to Day -1) to Follow-up visit (30 days after last dose of study drug ± 7 days)